When George Washington took command of the Continental Army in 1775, America was fighting a war on two fronts: one for independence from the British, and a second for survival against smallpox. Because Washington knew the ravages of the disease firsthand, he understood that the smallpox virus, then an invisible enemy, could cripple his army and end the war before it began.

That’s why Washington eventually made the bold decision to inoculate all American troops who had never been sickened with smallpox at a time when inoculation was a crude and often deadly process. His gamble paid off. The measure staved off smallpox long enough to win a years-long fight with the British. In the process, Washington pulled off the first massive, state-funded immunization campaign in American history.

In 1751, when Washington was 19 years old, he and his brother Lawrence sailed to Barbados in the hopes that the warm island air would cure his sickly sibling of tuberculosis. Just a day after landing, the brothers dined in the home of a wealthy local merchant, Gedney Clarke. In his diary, young Washington expressed some reservations.

“We went,—myself with some reluctance, as the smallpox was in his family,” wrote Washington.

Washington should have listened to his gut. Two weeks later, after the smallpox virus completed its incubation period, Washington was down for the count.

“Was strongly attacked with the small Pox,” was the last thing Washington wrote in his diary for 24 days. Even though his case was relatively mild, he would still have been bedridden for weeks, rocked by high fevers and chills, severe body aches, a twisted stomach and the telltale oozing rash.

Washington was lucky to escape with his life and few visible scars. In really bad cases, individual smallpox pustules ran together into a single pus-filled rash that seeped, cracked and sloughed off in large sheets. Those far more serious smallpox infections were often fatal or left the victim with hideous scars.

Fast forward to 1775, when Washington took the reins of a newly formed Continental Army laying siege to British-held Boston. That summer, smallpox was running rampant through Boston and one of Washington’s first orders of business was to safeguard his troops from a potentially debilitating outbreak.

“Washington knew what smallpox was like and he knew how it could incapacitate his Army,” says Elizabeth Fenn, a professor of early American history at the University of Colorado Boulder and author of Pox Americana: The Great Smallpox Epidemic of 1775-82.

Washington also knew that his American-born soldiers were far more susceptible to the disease than the European enemy. That’s because smallpox was endemic in England, meaning that a high percentage of British troops had already contracted the disease as children and now carried lifelong immunity.

In contrast, relatively few New Englanders and Southerners had ever been exposed to the virus. For example, only 23 percent of North Carolina soldiers who enlisted in 1777 had ever had smallpox.

Armed only with a primitive understanding of contagion and immunity, Washington had to decide between several anti-smallpox schemes, each with its own significant risks.

“It comes down to herd immunity,” says Fenn. “You either have to let people be exposed to the disease and naturally acquire immunity, which could be devastating for his troops and have devastating consequences for the war. Or somehow quarantine your troops, which means they’re not going to be able to fight. Or immunize them.”

But immunization in the 1770s was not what it’s like today with a single injection and a low risk of mild symptoms. Edward Jenner didn’t even develop his revolutionary cowpox-based vaccine for smallpox until 1796. The best inoculation technique at Washington’s disposal during the Revolutionary War was a nasty and sometimes fatal method called “variolation.”

“An inoculation doctor would cut an incision in the flesh of the person being inoculated and implant a thread laced with live pustular matter into the wound,” explains Fenn. “The hope and intent was for the person to come down with smallpox. When smallpox was conveyed in that fashion, it was usually a milder case than it was when it was contracted in the natural way.”

Variolization still had a case fatality rate of 5 to 10 percent. And even if all went well, inoculated patients still needed a month to recover. The procedure was not only risky for the individual patient but for the surrounding population. An inoculee with a mild case might feel well enough to walk around town, infecting countless others with potentially more serious infections.

When Washington weighed the risks at Boston in July 1775, he feared that a large-scale inoculation would sideline his troops, or worse, lead to a full-blown epidemic. So during the Siege of Boston, Washington opted for a strict quarantine of both sickened soldiers and civilians. Civilians showing smallpox symptoms were held in the town of Brookline, while military cases were sent to a quarantine hospital located at a pond near Cambridge.

“No Person is to be allowed to go to Fresh-water pond a fishing or on any other occasion as there may be a danger of introducing the smallpox into the army,” wrote Washington on July 4, 1775, his second official day as general.

The quarantine did its job, isolating the sick long enough for the British to surrender Boston. But as the fight for independence moved elsewhere, smallpox followed the American army like an unshakeable curse. Army life in the 18th century was cramped and unsanitary with new recruits mingling microbes with soldiers from entirely different parts of the country. Needless to say, smallpox thrived.

The virus proved a formidable enemy during the Battle of Quebec waged on December 31, 1775, in which the Continental Army was so weakened by smallpox that it had no option but retreat. As it turned out, the long march south from Canada through New York was almost worse than the battle as smallpox tore through the ranks.

“There are horrific accounts of men dying at a place called Île aux Noix at the northern tip of Lake Champlain with lice and fleas and maggots crawling all over them,” says Fenn. “It was just an awful, awful scene.”

There were even rumors circulating among American military leaders that the British were engaging in biowarfare, deliberately sending sick soldiers and civilians to infect the revolutionaries. While there’s no smoking-gun evidence that such a plot was carried out, it wasn’t without precedent.

“There’s that famous event at Fort Pitt during Pontiac’s uprising in 1763 in which several different British officers, including Jeffery Amhurst, came up with the idea of deliberately conveying smallpox to enemies and implementing it,” says Fenn. “This was not a novel idea during the Revolutionary War.”

By the time America officially declared its independence on July 4, 1776, the effectiveness of quarantine was thrown into doubt and there was no easy way of calculating the risk of a mass inoculation of the beleaguered American troops.

“The small Pox! The small Pox!” John Adams wrote to his wife, Abigail. “What shall We do with it?”

By the following winter, Washington and his troops were camped in Morristown, New Jersey, where the threat of smallpox was as dire as ever. America’s stoic general waffled back and forth on whether to inoculate or not, even making the mass inoculation order and then rescinding it. Finally, on February 5, 1777, he made the call in a letter to John Hancock, president of the Second Continental Congress.

“The small pox has made such Head in every Quarter that I find it impossible to keep it from spreading thro’ the whole Army in the natural way. I have therefore determined, not only to innoculate all the Troops now here, that have not had it, but shall order Docr. Shippen to innoculate the Recruits as fast as they come in to Philadelphia.”

Fenn says that inoculating all troops without natural smallpox immunity was a daunting task. First, medical personnel had to examine each individual to determine if they had contracted the disease in the past, then they conducted the risky variolation procedure, followed by a month-long recovery process attended by teams of nurses.

Meanwhile, this entire process—the first of its kind and scale—had to be conducted in total secrecy. If the British caught wind that large numbers of American soldiers were laid up in bed with smallpox, it could be the end.

“I need not mention the necessity of as much secrecy as the nature of the Subject will admit of,” wrote Washington, “it being beyond doubt, that the Enemy will avail themselves of the event as far as they can.”

Thankfully for the Americans, the 1777 inoculations in Philadelphia went off without a hitch and without tipping off the British. Even more remarkable was that a second major round of smallpox inoculations was conducted in the middle of the infamously unforgiving winter of 1778 when Washington’s troops were quartered at Valley Forge.

“Notwithstanding the Orders I had given last year to have all the Recruits innoculated, I found upon examination, that between three and four thousand Men had not had the Small Pox,” wrote Washington in January 1778, “That disorder began to make its appearance in Camp, and to avoid its spreading in the natural way, the whole were immediately innoculated.”

It’s hard enough to imagine the deprivations that Continental soldiers experienced during that bitter cold Pennsylvania, but almost impossible to think that many of them also willingly contracted smallpox during the grueling episode.

“It was one of the things that made that Valley Forge winter of 1778 so difficult,” says Fenn. “We’re all familiar with the bloody footprints in the snow, and the shortages of food and clothing. Add to that the fact that soldiers who had not had smallpox also underwent inoculation that winter.”

By the spring of 1778, the ranks of the Continental army swelled with smallpox-immune recruits ready to take the fight to the British. And while Washington’s risky decision to inoculate the whole army against smallpox didn’t win the war by itself, Fenn believes it deserves a place among the most important deciding factors in the American victory.

“The general,” she writes in Pox Americana, “had outflanked his enemy.”